Standard solid-phase immunoassays with antibodies involve the formation of a complex between an antibody adsorbed/immobilized on a solid phase (capture antibody), the antigen, and an antibody to another epitope of the antigen conjugated with an enzyme or detectable label (tracer antibody). In the assay, a sandwich is formed: solid phase/capture antibody/antigen/tracer antibody. In the reaction catalyzed by the sandwich among other things the activity of the antibody-conjugated enzyme is proportional to the antigen concentration in the incubation medium. Anti-idiotypic antibody assays are mentioned, for example, in U.S. Pat. No. 5,219,730; WO 87/002778; EP 0 139 389; and EP 0 170 302. Wadhwa, M., et al. (J. Immunol. Methods 278 (2003) 1-17) report strategies for the detection, measurement and characterization of unwanted antibodies induced by therapeutic biologicals. A method for producing anti idiotypic antibodies is reported in EP 1 917 854.
Chen, Y.-P., et al. (Clin. Vac. Immunol. 14 (2007) 720-725) report the rapid detection of hepatitis B virus surface antigen by an agglutination assay mediated by a bispecific diabody against both human erythrocytes and hepatitis B virus surface antigen. Porter, R., et al report an electro-active system of immuno-assay (EASI assay) utilizing self-assembled monolayer modified electrodes (Biosensors Bioelec. 16 (2001) 9-12). The development of an enzyme immunoassay for the measurement of human tumor necrosis factor-alpha (hTNF-alpha) using bispecific antibodies to hTNF-alpha and horseradish peroxidase is reported by Berkova, N., et al. (Biotechnol. Appl. Biochem. 23 (1996) 163-171). In EP 0 962 771 a detection apparatus and method for the same is reported. Reinhartz, H. W., et al. (Analyst 121 (1996) 767-771) report bispecific multivalent antibody studied by real-time interaction analysis for the development of an antigen-inhibition enzyme-linked immunosorbent assay. The chemical generation of bispecific antibodies is reported by Doppalapudi, V. R., et al. (Proc. Natl. Acad. Sci. 107 (2010) 22611-22616).